Discoid lupus erythematosus

Summary

Discoid lupus erythematosus (MONDO:0019558) is a disease with 1 cohort gene and 16 clinical trials. Top therapeutic interventions include apremilast, artenimol, and betamethasone valerate.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 10
• Clinical trials: 16

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	30	Worldwide	Validated
Annual incidence	1-9 / 100 000	3.56	United States	Validated
Annual incidence	1-9 / 100 000	3.2	Sweden	Validated

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0001010	Hypopigmentation of the skin	Frequent (30-79%)
HP:0001075	Atrophic scars	Frequent (30-79%)
HP:0004552	Scarring alopecia of scalp	Frequent (30-79%)
HP:0007502	Follicular hyperkeratosis	Frequent (30-79%)
HP:0025474	Erythematous plaque	Frequent (30-79%)
HP:0030350	Erythematous papule	Frequent (30-79%)
HP:0100585	Telangiectasia of the skin	Frequent (30-79%)
HP:4000107	Positive lupus band test	Frequent (30-79%)
HP:0002829	Arthralgia	Occasional (5-29%)
HP:0006739	Squamous cell carcinoma of the skin	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	discoid lupus erythematosus
Mondo ID	MONDO:0019558
MeSH	D008179
Orphanet	90281
ICD-10-CM	L93.0
ICD-11	2144907708
NCIT	C26820
SNOMED CT	200938002
UMLS	C5574816
MedGen	1811126
GARD	0019131
MedDRA	10013072
Is cancer (heuristic)	no

Also known as: DLE

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › rheumatic disorder › lupus erythematosus › cutaneous lupus erythematosus › chronic cutaneous lupus erythematosus › discoid lupus erythematosus

Related subtypes (4): chilblain lupus, hypertrophic or verrucous lupus erythematosus, lupus erythematosus tumidus, lupus erythematosus panniculitis

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
812084	NM_147686.4(TRAF3IP2):c.1286C>A (p.Thr429Asn)	TRAF3IP2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRAF3IP2	Orphanet:1334	Chronic mucocutaneous candidiasis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRAF3IP2	HGNC:1343	ENSG00000056972	O43734	E3 ubiquitin ligase TRAF3IP2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAF3IP2	E3 ubiquitin ligase TRAF3IP2	E3 ubiquitin ligase that catalyzes ‘Lys-63’-linked polyubiquitination of target protein, enhancing protein-protein interaction and cell signaling.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRAF3IP2	Other/Unknown	no		SEFIR_dom, E3_ubiq_ligase_TRAF3IP2

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
oocyte	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAF3IP2	266	ubiquitous	marker	cartilage tissue, oocyte, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRAF3IP2	1,463

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRAF3IP2	O43734	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
transitional two stage B cell differentiation	1	16852.0×	1e-03	TRAF3IP2
eosinophil mediated immunity	1	16852.0×	1e-03	TRAF3IP2
B cell affinity maturation	1	8426.0×	1e-03	TRAF3IP2
protein localization to P-body	1	8426.0×	1e-03	TRAF3IP2
leukocyte activation involved in inflammatory response	1	5617.3×	1e-03	TRAF3IP2
eosinophil homeostasis	1	5617.3×	1e-03	TRAF3IP2
T-helper 17 type immune response	1	3370.4×	0.001	TRAF3IP2
interleukin-17A-mediated signaling pathway	1	2808.7×	0.001	TRAF3IP2
establishment of T cell polarity	1	1872.4×	0.002	TRAF3IP2
type 2 immune response	1	1872.4×	0.002	TRAF3IP2
CD40 signaling pathway	1	1685.2×	0.002	TRAF3IP2
interleukin-17-mediated signaling pathway	1	1685.2×	0.002	TRAF3IP2
B cell apoptotic process	1	1404.3×	0.002	TRAF3IP2
mucus secretion	1	1296.3×	0.002	TRAF3IP2
neutrophil activation	1	991.3×	0.002	TRAF3IP2
lymph node development	1	802.5×	0.003	TRAF3IP2
signal transduction involved in regulation of gene expression	1	702.2×	0.003	TRAF3IP2
B cell homeostasis	1	561.7×	0.003	TRAF3IP2
positive regulation of defense response to virus by host	1	526.6×	0.003	TRAF3IP2
skin development	1	443.5×	0.004	TRAF3IP2
spleen development	1	401.2×	0.004	TRAF3IP2
T cell differentiation	1	383.0×	0.004	TRAF3IP2
mRNA stabilization	1	366.4×	0.004	TRAF3IP2
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.004	TRAF3IP2
humoral immune response	1	280.9×	0.005	TRAF3IP2
protein K63-linked ubiquitination	1	267.5×	0.005	TRAF3IP2
protein import into nucleus	1	144.0×	0.008	TRAF3IP2
kidney development	1	140.4×	0.008	TRAF3IP2
heart development	1	78.8×	0.014	TRAF3IP2
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.015	TRAF3IP2

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Delgocitinib, Ruxolitinib, Secukinumab, Thalidomide.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRAF3IP2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TRAF3IP2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TRAF3IP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 16.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	10
Not specified	3
EARLY_PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06261021	PHASE2	RECRUITING	Study to Evaluate the Efficacy of Ruxolitinib 1.5% Cream in Adult Subjects with Discoid Lupus Erythematosus
NCT07557927	PHASE2	NOT_YET_RECRUITING	A Multicentre, Randomised, Double-blind, Positive-control Clinical Trial Evaluating Dihydroartemisinin Tablets for the Treatment of Discoid Lupus Erythematosus
NCT00001680	PHASE2	COMPLETED	A Pilot Trial of Topical Thalidomide for the Management of Chronic Discoid Lupus Erythematosus
NCT00625157	PHASE2	COMPLETED	Efficacy and Safety of ASF-1096 Cream 0.5% in the Treatment of Discoid Lupus Erythematosus (DLE) Lesions (2)
NCT00625521	PHASE2	COMPLETED	Efficacy and Safety of ASF-1096 Cream 0.5% in the Treatment of Discoid Lupus Erythematosus (DLE) Lesions
NCT00708916	PHASE1/PHASE2	COMPLETED	Safety Study of Clinical and Immune Effects of Phosphodiesterase 4 (PDE-4) Inhibitor in Cutaneous Lupus Patients
NCT00797784	PHASE2	UNKNOWN	The Safety and Efficacy of Etanercept (Enbrel®) for the Treatment of Discoid Lupus Erythematosus
NCT03866317	PHASE2	WITHDRAWN	A Study to Assess the Safety and Efficacy of Secukinumab in Alleviating Symptoms of Discoid Lupus Erythematosus
NCT03958955	PHASE2	TERMINATED	Efficacy and Safety of Delgocitinib Cream in Discoid Lupus Erythematosus.
NCT04908280	PHASE2	COMPLETED	Study of Ruxolitinib Cream for the Treatment of Discoid Lupus Erythematosus
NCT05591222	PHASE2	TERMINATED	Study of Daxdilimab (HZN-7734) in Participants With Moderate-to-Severe Primary Discoid Lupus Erythematosus
NCT03159936	EARLY_PHASE1	TERMINATED	Oral Tofacitinib in Adult Subjects With Discoid Lupus Erythematosus (DLE) and Systemic Lupus Erythematosus (SLE)
NCT05362188	EARLY_PHASE1	COMPLETED	Topical Nicotinamide in Treatment of DLE
NCT00608673	Not specified	COMPLETED	Comparing the Therapeutic Efficacy of Pimecrolimus Cream With Betamethasone Cream for Discoid Lupus Erythematosus
NCT00691769	Not specified	COMPLETED	Expression of Fas Protein in Skin Biopsies of Participants With Scarring Alopecia
NCT02125695	Not specified	COMPLETED	Pilot Tape Harvesting Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
APREMILAST	4	1
ARTENIMOL	4	1
BETAMETHASONE VALERATE	4	1
NIACINAMIDE	4	1
PIMECROLIMUS	4	1
THALIDOMIDE	4	1
ARTEMISININ	3	1
DELGOCITINIB	3	1
DAXDILIMAB	2	1
CHEMBL426123	0	1
CHEMBL5421204	0	1
CHEMBL3932056	0	1
CHEMBL470034	0	1
CHEMBL511326	0	1
CHEMBL5178921	0	1
CHEMBL5206150	0	1
CHEMBL5284664	0	1
CHEMBL5288857	0	1